Clonal expansions in acute EBV infection are detectable in the CD8 and notthe CD4 subset and persist with a variable CD45 phenotype

We have applied a sensitive global analysis of TCR heterogeneity to compare clonal dynamics of CD4(+) and CD8(+) T cells in acute infectious mononucle osis, Using this approach, we are able to identify a broad representation o f the total virus-specific population without the bias of in vitro culture and then to track their phenotype and fate by their unique molecular footpr int, We demonstrate a large number of Ag-driven clones using different TCRs in the acute phase, all CD8(+), The diverse large clones generated in the CD8 subset in response to this virus contrast with the complete lack of det ectable clonal expansion in the CD4 compartment, Many of the same clones re main detectable in directly ex vivo CD8(+) T cells for at least a year afte r resolution of infectious mononucleosis, although the clone size is reduce d. Thus, memory CDS cells following EBV infection persist at relatively hig h circulating frequency and represent a subset of the large range of clonot ypes comprising the acute effecters, Separation of samples into CD45RA (nai ve) and CD45RO (memory) fractions shows the accumulation of identical CDR3 region defined clonotypes in both CD45RO and CD45RA fractions and sequencin g confirms that dominant long-lived monoclonal expansions can reside in the CD45RA pool.